PMID- 22710353
OWN - NLM
STAT- MEDLINE
DCOM- 20121119
LR  - 20221207
IS  - 1873-7064 (Electronic)
IS  - 0028-3908 (Linking)
VI  - 63
IP  - 2
DP  - 2012 Aug
TI  - Early intervention with fluoxetine reverses abnormalities in the serotonergic 
      system and behavior of rats exposed prenatally to dexamethasone.
PG  - 292-300
LID - 10.1016/j.neuropharm.2012.03.027 [doi]
AB  - Many psychiatric disorders emerge after adolescence. Among a variety of 
      predisposing factors, prenatal stress has been thought to cause the symptoms of 
      anxiety disorders. We recently reported that prenatal dexamethasone (DEX) 
      exposure, which mimics some aspects of prenatal stress, induced anxiety-related 
      behaviors in male offspring when they reached adulthood. Before the emergence of 
      behavioral changes, abnormalities occurred in the hypothalamic-pituitary-adrenal 
      axis during postnatal development. In the present study, we found abnormalities 
      in serotonin (5-HT) signaling, including decreased expression of 5-HT(1A) 
      receptor (5-HT(1A)-R) mRNA in the medial prefrontal cortex (mPFC) and 5-HT 
      content in the hippocampus at postnatal week (PW) 4. These results support using 
      early therapeutic interventions with serotonergic drugs to prevent late-emerging 
      anxiety symptoms. To test this hypothesis, we treated rat pups born to 
      DEX-administered mothers with fluoxetine (FLX), a selective serotonin reuptake 
      inhibitor commonly used as an anti-anxiety medication, via breast milk from 
      postnatal day (PD) 2-21. Anxiety-related behaviors examined at PW11-13 were not 
      observed in the prenatally DEX-exposed offspring that were treated with FLX. 
      Likewise, FLX increased 5-HT concentrations in the mPFC and ventral hippocampus 
      at PW3 and normalized 5-HT(1A)-R mRNA concentrations in the mPFC at PW4. The 
      decrease in brain-derived neurotrophic factor (BDNF) protein in the mPFC and 
      dorsal hippocampus was also restored at PW4. Furthermore, administration of the 
      5-HT(1A)-R full agonist (R)-(+)-8-hydroxy-2-(di-n-propylamino)tetralin from PD2 
      to 21 also prevented the emergence of behavioral abnormalities in the prenatally 
      DEX-exposed offspring, implicating the involvement of 5-HT(1A)-Rs in the neonatal 
      FLX effect. Collectively, an early pharmacological intervention to normalize 
      serotonergic transmission effectively suppressed the emergence of symptoms 
      induced by prenatal DEX exposure in rats.
CI  - Copyright (c) 2012 Elsevier Ltd. All rights reserved.
FAU - Nagano, Masatoshi
AU  - Nagano M
AD  - Department of Pharmacology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, 
      Tokyo 113-8602, Japan. nagano@nms.ac.jp
FAU - Liu, Mingyan
AU  - Liu M
FAU - Inagaki, Hirofumi
AU  - Inagaki H
FAU - Kawada, Tomoyuki
AU  - Kawada T
FAU - Suzuki, Hidenori
AU  - Suzuki H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120413
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Glucocorticoids)
RN  - 0 (Serotonin Uptake Inhibitors)
RN  - 01K63SUP8D (Fluoxetine)
RN  - 333DO1RDJY (Serotonin)
RN  - 7S5I7G3JQL (Dexamethasone)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/*drug effects
MH  - Dexamethasone/*pharmacology
MH  - *Early Medical Intervention
MH  - Female
MH  - Fluoxetine/pharmacology/*therapeutic use
MH  - Glucocorticoids/*pharmacology
MH  - Hippocampus/drug effects/metabolism
MH  - Hypothalamo-Hypophyseal System/drug effects/metabolism
MH  - Male
MH  - Motor Activity/drug effects
MH  - Pituitary-Adrenal System/drug effects/metabolism
MH  - Prefrontal Cortex/drug effects/metabolism
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/*drug therapy/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Serotonin/*metabolism
MH  - Selective Serotonin Reuptake Inhibitors/pharmacology/*therapeutic use
EDAT- 2012/06/20 06:00
MHDA- 2012/12/10 06:00
CRDT- 2012/06/20 06:00
PHST- 2011/07/08 00:00 [received]
PHST- 2012/03/29 00:00 [revised]
PHST- 2012/03/31 00:00 [accepted]
PHST- 2012/06/20 06:00 [entrez]
PHST- 2012/06/20 06:00 [pubmed]
PHST- 2012/12/10 06:00 [medline]
AID - S0028-3908(12)00136-0 [pii]
AID - 10.1016/j.neuropharm.2012.03.027 [doi]
PST - ppublish
SO  - Neuropharmacology. 2012 Aug;63(2):292-300. doi: 10.1016/j.neuropharm.2012.03.027. 
      Epub 2012 Apr 13.